CYCLOIDEA-like genes control floral symmetry, floral orientation, and nectar guide patterning.

Actinomorphic flowers usually orient vertically (relative to the horizon) and possess symmetric nectar guides, while zygomorphic flowers often face horizontally and have asymmetric nectar guides, indicating that floral symmetry, floral orientation, and nectar guide patterning are correlated. The origin of floral zygomorphy is dependent on the dorsoventrally asymmetric expression of CYCLOIDEA (CYC)-like genes. However, how horizontal orientation and asymmetric nectar guides are achieved remains poorly understood. Here, we selected Chirita pumila (Gesneriaceae) as a model plant to explore the molecular bases for these traits. By analyzing gene expression patterns, protein-DNA and protein-protein interactions, and encoded protein functions, we identified multiple roles and functional divergence of 2 CYC-like genes, i.e. CpCYC1 and CpCYC2, in controlling floral symmetry, floral orientation, and nectar guide patterning. CpCYC1 positively regulates its own expression, whereas CpCYC2 does not regulate itself. In addition, CpCYC2 upregulates CpCYC1, while CpCYC1 downregulates CpCYC2. This asymmetric auto-regulation and cross-regulation mechanism might explain the high expression levels of only 1 of these genes. We show that CpCYC1 and CpCYC2 determine asymmetric nectar guide formation, likely by directly repressing the flavonoid synthesis-related gene CpF3'5'H. We further suggest that CYC-like genes play multiple conserved roles in Gesneriaceae. These findings shed light on the repeated origins of zygomorphic flowers in angiosperms.

Application of metagenomic next-generation sequencing in the clinical diagnosis of infectious diseases after allo-HSCT: a single-center analysis.

BACKGROUND: We investigated the value of metagenomic next-generation sequencing (mNGS) in diagnosing infectious diseases in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Fifty-four patients who had fever following allo-HSCT from October 2019 to February 2022 were enrolled. Conventional microbiological tests (CMTs) and mNGS, along with imaging and clinical manifestations, were used to diagnose infection following allo-HSCT. The clinical diagnostic value of mNGS was evaluated. RESULTS: A total of 61 mNGS tests were performed, resulting in the diagnosis of 46 cases of infectious diseases. Among these cases, there were 22 cases of viral infection, 13 cases of fungal infection, and 11 cases of bacterial infection. Moreover, 27 cases (58.7%) were classified as bloodstream infections, 15 (32.6%) as respiratory infections, 2 (4.3%) as digestive system infections, and 2 (4.3%) as central nervous system infections. Additionally, there were 8 cases with non-infectious diseases (8/54, 14.81%), including 2 cases of interstitial pneumonia, 2 cases of bronchiolitis obliterans, 2 cases of engraftment syndrome, and 2 cases of acute graft-versus-host disease. The positive detection rates of mNGS and CMT were 88.9% and 33.3%, respectively, with significant differences (P < 0.001). The sensitivity of mNGS was 97.82%, the specificity was 25%, the positive predictive value was 93.75%, and the negative predictive value was 50%. Following treatment, 51 patients showed improvement, and 3 cases succumbed to multidrug-resistant bacterial infections. CONCLUSIONS: mNGS plays an important role in the early clinical diagnosis of infectious diseases after allo-HSCT, which is not affected by immunosuppression status, empiric antibiotic therapy, and multi-microbial mixed infection.

Fecal microbiota transplantation: Emerging applications in autoimmune diseases.

Both genetic susceptibility and environmental factors are important contributors to autoimmune disease pathogenesis. As an environmental factor, the gut microbiome plays a crucial role in the development and progression of autoimmune diseases. Thus, strategies targeting gut microbiome alterations can potentially be used to treat autoimmune disease. Microbiota-based interventions, such as prebiotics, probiotics, dietary interventions, and fecal microbiota transplantation (FMT), have attracted growing interest as novel treatment approaches. FMT is an effective method for treating recurrent Clostridioides difficile infections; moreover, it is emerging as a promising treatment for patients with inflammatory bowel disease and other autoimmune diseases. Although the mechanisms underpinning the interaction between the gut microbiome and host are not fully understood in patients with autoimmune disease, FMT has been shown to restore altered gut microbiota composition, rebuild the intestinal microecosystem, and mediate innate and adaptive immune responses to achieve a therapeutic effect. In this review, we provide an overview of FMT and discuss how FMT can be used as a novel treatment approach for autoimmune diseases. Furthermore, we discuss recent challenges and offer future research directions.

Photoluminescent Properties and Mechanism of Novel Cyanine-Borondifluoride Curcuminoid Hybrids as Red-to-Near Infrared and Endoplasmic Reticulum-Targeting Dyes.

Synthesis-oriented design led us to the discovery of a series of novel cyanine-borondifluoride curcuminoid hybrids called Nanchang Red (NCR) dyes that overcome the intrinsic low synthetic yields of symmetrical cyanine-difluoroboronate (BF2 )-hybridized NIR dyes. The hybridization endows NCR dyes with high molar extinction coefficients, efficient red-to-NIR emission, and enlarged Stokes shifts. Quantum chemical calculations revealed that the asymmetrical layout of the three key electron-withdrawing and electron-donating fragments results in a special pattern of partial charge separation and inconsistent degrees of charge delocalization on their π-conjugated backbones. While the nature of the hemicyanine fragment exerts significant influence on the excitation modes of NCR dyes, the borondifluoride hemicurcuminoid fragment is the major contributor to the enlarged Stokes shifts. Cell imaging experiments illustrated that a subtle change in the N-heterocycle of the hemicyanine fragment has a remarkable effect on the subcellular localization of NCR dyes. Unlike other previously reported cyanine-BF2 hybridized dyes, which mainly target mitochondria, the benzothiazole and indole-based NCR dyes accumulate in both the endoplasmic reticulum (ER) and lipid droplets of HeLa cells, whereas the benzoxazole and quinoline-based NCR dyes stain the ER specifically.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

AIM: To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes. MATERIALS AND METHODS: We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n = 1627 and n = 2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings. RESULTS: A total of 3989 patients were randomized to undergo intensive (n = 1984) or standard SBP treatment (n = 2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses. CONCLUSIONS: An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Roles of Abscisic Acid and Gibberellins in Stem/Root Tuber Development.

Root and tuber crops are of great importance. They not only contribute to feeding the population but also provide raw material for medicine and small-scale industries. The yield of the root and tuber crops is subject to the development of stem/root tubers, which involves the initiation, expansion, and maturation of storage organs. The formation of the storage organ is a highly intricate process, regulated by multiple phytohormones. Gibberellins (GAs) and abscisic acid (ABA), as antagonists, are essential regulators during stem/root tuber development. This review summarizes the current knowledge of the roles of GA and ABA during stem/root tuber development in various tuber crops.

Molecular characterization of Cyprinid herpesvirus 3 encoded viral interleukin10.

Cyprinid herpesvirus 3 (CyHV-3), a virus that encodes an interleukin10 (IL-10) homologue, causes severe economic losses to the common carp and koi culture industry. The present study was devoted to this IL-10 homologue. Recombinant viral IL-10 (vIL-10) protein encoded by CyHV-3 ORF134 gene using prokaryotic expression system was obtained successfully. Bioinformatics analysis revealed that the amino acid sequence of CyHV-3 vIL-10 has low homology with other host IL-10 or viruses encoded IL-10s. However, their tertiary structure is quite similar, suggesting conservative biological functions between IL-10s and vIL-10s. The biological activity of CyHV-3 vIL-10 was detected by using CCK-8 kit and real time quantitative PCR. The results showed that CyHV-3 vIL-10 down regulate epithelioma papulosum cyprini (EPC) cellular activity at 72 h. Moreover, CyHV-3 vIL-10 inhibits the LPS-induced expression of proinflammatory genes, similar to common carp IL-10. Altogether, the results of this study demonstrate that a clear biological activity of CyHV-3 vIL-10 on its host cells and indicates CyHV-3 vIL-10 may play an important role in viral immune evasion.

Peptidyl-prolyl isomerase Pin1 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation in ApoE-/- mice.

Peptidyl-prolyl isomerase Pin1 has been reported to be associated with endothelial dysfunction. However, the role of smooth muscle Pin1 in the vascular system remains unclear. Here, we examined the potential function of Pin1 in smooth muscle cells (SMCs) and its contribution to abdominal aortic aneurysm (AAA) pathogenesis. The level of Pin1 expression was found to be elevated in human AAA tissues and mainly localized to SMCs. We constructed smooth muscle-specific Pin1 knockout mice to explore the role of this protein in AAA formation and to elucidate the underlying mechanisms. AAA formation and elastin degradation were hindered by Pin1 depletion in the angiotensin II-induced mouse model. Pin1 depletion reversed the angiotensin II-induced pro-inflammatory and synthetic SMC phenotype switching via the nuclear factor (NF)-κB p65/Klf4 axis. Moreover, Pin1 depletion inhibited the angiotensin II-induced matrix metalloprotease activities. Mechanically, Pin1 deficiency destabilized NF-κB p65 by promoting its polyubiquitylation. Further, we found STAT1/3 bound to the Pin1 promoter, revealing that activation of STAT1/3 was responsible for the increased expression of Pin1 under angiotensin II stimulation. Thus, these results suggest that Pin1 regulates pro-inflammatory and synthetic SMC phenotype switching and could be a novel therapeutic target to limit AAA pathogenesis.

The BET/BRD inhibitor JQ1 attenuates diabetes-induced cognitive impairment in rats by targeting Nox4-Nrf2 redox imbalance.

Diabetes-induced oxidative damage is believed to play an important role in the development of cognitive dysfunction. In this study, the involvement of the Nox4-Nrf2 redox imbalance was investigated. STZ-induced diabetic rats exhibited obvious oxidative stress and apoptosis in the hippocampus assessed by augmentation of lipid peroxidation, positive TUNEL staining, elevated ratio of Bax/Bcl-2 and increased caspase 3 activity. Furthermore, hyperglycemia markedly increased Nox4 activity and reduced the activation of Nrf2 by suppressing its up-stream regulatory Akt as well as down-stream target HO-1. Significant improvement of cognitive performance was observed after treatment with the BET/BRD inhibitor JQ1, accompanied by decreased oxidative stress, neuroinflammation and apoptosis in the hippocampus. JQ1 treatment also improved changes in the neuronal cell morphology as well as increased the expression of p-AKT, Nrf2 and HO-1. Our results provide evidence indicating that JQ1 treatment could modulate Nox4-Nrf2 redox imbalance in the hippocampus and may be a promising agent for diabetes-associated cognitive dysfunction.

The Role of Psychological Stress on Heart Autophagy in Mice With Heart Failure.

OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. METHODS: C57BL/6 mice underwent transverse aortic constriction, with or without combined acoustic and restraint stress, and cardiac function was assessed by echocardiography analysis. Serum corticosterone and angiotensin II (Ang II) were determined using enzyme-linked immunosorbent assay (ELISA). Autophagy and oxidative stress were measured with immunohistochemistry and quantitative polymerase chain reaction, and chloroquine and rapamycin were used to detect autophagy flux. In vivo, cardiomyocytes were cultured with or without Ang II or N-acetylcysteine, and autophagy and oxidative stress were also detected. RESULTS: A 1-week stress exposure significantly increased serum levels of corticosterone and Ang II (p = .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (p = .002). Furthermore, stress exposure unregulated messenger RNA expression of Bcl-2-interacting coiled-coil protein 1 (10.891 [3.029] versus 4.754 [1.713], p = .001), cysteine-rich domain containing beclin-1 interacting (6.403 [1.813] versus 3.653 [0.441], p = .006), and autophagy 7 (111.696 [4.049] versus 6.189 [1.931], p = .017), increased expression of autophagosomal, and decreased clearance of autophagosomes. In vitro, Ang II significantly increased autophagy flux in cultured cardiomyocytes, which could be partly inhibited by N-acetylcysteine. CONCLUSIONS: Psychological stress may contribute to the development of CHF by enhancing heart oxidative stress and impairing autophagy flux.

Insights from lncRNAs Profiling of MIN6 Beta Cells Undergoing Inflammation.

Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease characterized by chronic and progressive apoptotic destruction of pancreatic beta cells. During the initial phases of T1DM, cytokines and other inflammatory mediators released by immune cells progressively infiltrate islet cells, induce alterations in gene expression, provoke functional impairment, and ultimately lead to apoptosis. Long noncoding RNAs (lncRNAs) are a new important class of pervasive genes that have a variety of biological functions and play key roles in many diseases. However, whether they have a function in cytokine-induced beta cell apoptosis is still uncertain. In this study, lncRNA microarray technology was used to identify the differently expressed lncRNAs and mRNAs in MIN6 cells exposed to proinflammatory cytokines. Four hundred forty-four upregulated and 279 downregulated lncRNAs were detected with a set filter fold-change ≧2.0. To elucidate the potential functions of these lncRNAs, Gene Ontology (GO) and pathway analyses were used to evaluate the potential functions of differentially expressed lncRNAs. Additionally, a lncRNA-mRNA coexpression network was constructed to predict the interactions between the most strikingly regulated lncRNAs and mRNAs. This study may be utilized as a background or reference resource for future functional studies on lncRNAs related to the diagnosis and development of new therapies for T1DM.

Development and validation of the coronary heart disease scale under the system of quality of life instruments for chronic diseases QLICD-CHD: combinations of classical test theory and Generalizability Theory.

BACKGROUND: Quality of life (QOL) for patients with coronary heart disease (CHD) is now concerned worldwide with the specific instruments being seldom and no one developed by the modular approach. OBJECTIVES: This paper is aimed to develop the CHD scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-CHD) by the modular approach and validate it by both classical test theory and Generalizability Theory. METHODS: The QLICD-CHD was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, pre-testing and quantitative statistical procedures. 146 inpatients with CHD were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t-tests and also G studies and D studies of Genralizability Theory analysis. RESULTS: Multi-trait scaling analysis, correlation and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. The internal consistency α and test-retest reliability coefficients (Pearson r and Intra-class correlations ICC) for the overall instrument and all domains were higher than 0.70 and 0.80 respectively; The overall and all domains except for social domain had statistically significant changes after treatments with moderate effect size SRM (standardized response mea) ranging from 0.32 to 0.67. G-coefficients and index of dependability (Ф coefficients) confirmed the reliability of the scale further with more exact variance components. CONCLUSIONS: The QLICD-CHD has good validity, reliability, and moderate responsiveness and some highlights, and can be used as the quality of life instrument for patients with CHD. However, in order to obtain better reliability, the numbers of items for social domain should be increased or the items' quality, not quantity, should be improved.

Remnant cholesterol and intensive blood pressure control in older patients with hypertension: a post hoc analysis of the STEP randomized trial†.

AIMS: Emerging evidence shows a close relationship between remnant cholesterol (RC) and hypertension. However, it is unknown whether RC is associated with the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes. METHODS AND RESULTS: We performed a post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants were randomly allocated to intensive (110 to <130 mmHg) or standard (130 to <150 mmHg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or cardiovascular death), the components thereof, and all-cause mortality were analysed by the tertile of baseline RC (lowest, middle, and highest). We followed 8206 patients for 3.33 years (median). The adjusted hazard ratios (HRs) [95% confidence interval (CI)] for the primary outcome were 1.06 (0.73-1.56), 0.58 (0.38-0.87), and 0.67 (0.46-0.96) in the lowest, middle, and highest RC tertiles, respectively (P for interaction = 0.11). However, significant heterogeneity in the treatment effects was observed when comparing the upper two tertiles with the lowest tertile (P for interaction = 0.033). For all-cause mortality, the adjusted HRs (95% CI) were 2.48 (1.30-4.73), 1.37 (0.71-2.65), and 0.42 (0.22-0.80) in the lowest, middle, and highest RC tertiles, respectively (P for interaction <0.0001). CONCLUSION: Baseline RC concentrations were associated with the effects of intensive SBP lowering on the primary composite cardiovascular outcome and all-cause mortality in hypertensive patients. These results are hypothesis-generating and merit further study. REGISTRATION: STEP ClinicalTrials.gov number: NCT03015311.

In our post hoc analysis of the STEP trial, baseline remnant cholesterol (RC) concentrations were associated with the effects of intensive systolic blood pressure (SBP) lowering on the primary composite cardiovascular outcome and all-cause mortality in hypertensive patients.Patients with a higher RC experienced greater cardiovascular benefits from intensive SBP lowering, while a lower RC was associated with attenuated benefits or even negative effects of intensive SBP lowering. These results are hypothesis-generating and merit further study.If confirmed, RC measurements could permit the identification of a subset of patients with high RC and hypertension, who may receive greater benefit from intensive SBP lowering to <130 mmHg.

Metagenomic Next-Generation Sequencing (mNGS) of cerebrospinal fluid for diagnosis of human herpesvirus 6B encephalitis following transplantation for severe aplastic anemia.

INTRODUCTION: Human herpesvirus 6B (HHV-6B) encephalitis is common in immunosuppressed patients and presents a diagnostic challenge for physicians. Metagenomic next-generation sequencing (mNGS) may facilitate early diagnosis of HHV-6B encephalitis. Herein, we described a case of HHV-6B encephalitis following transplantation for severe aplastic anemia (SAA) diagnosed by mNGS. CASE SUMMARY: A 31-year-old male underwent myeloablative haploid hematopoietic stem cell transplantation for the treatment of SAA. On day + 21 after transplantation, the patient developed symptoms such as sudden epilepsy, drowsiness, memory dislocation, and memory loss. HHV-6B encephalitis was confirmed based on cranial MRI and mNGS of cerebrospinal fluid. Following antiviral therapy with sodium foscarnet, the symptoms improved and HHV-6B was negative by mNGS. There were no serious sequelae. Currently, the patient is in good health and is still under follow-up. CONCLUSIONS: A case of HHV-6B encephalitis after SAA transplantation was diagnosed by mNGS of cerebrospinal fluid in time and was effectively treated with sodium foscarnet.

Mitigation of biofouling in membrane bioreactors by quorum-quenching bacteria during the treatment of metal-containing wastewater.

Quorum quenching (QQ) is an efficient way to mitigate membrane biofouling in a membrane bioreactor (MBR) during wastewater treatment. A QQ bacterium, Lysinibacillus sp. A4, was isolated and used to mitigate biofouling in an MBR during the treatment of wastewater containing metals. A QQ enzyme (named AilY) was cloned from A4 and identified as a metallo-ß-lactamase-like lactonase. The QQ activity of A4 and that of Escherichia coli BL21 (DE3) overexpressing AilY could be promoted by Fe2+, Mn2+, and Zn2+ while remaining unaffected by other metals tested. The two bacteria effectively mitigated biofouling by reducing the transmembrane pressure from around 30 to 20 kPa without negative influence on the COD, NH4+-N, or total phosphorus of the effluent. The relative abundance of Lysinibacillus sp. A4 increased greatly from 0.04 to 8.29% in the MBR with metal-containing wastewater, suggesting that Lysinibacillus sp. A4 could multiply quickly and adapt to this environment. Taken together, the findings suggested that A4 could tolerate metal to a certain degree, and this property could allow A4 to adapt well to metal-containing wastewater, making it a valuable strain for mitigating biofouling in MBR during the treatment of metal-containing wastewater.

Modifying soil bacterial communities in saline mudflats with organic acids and substrates.

Aims: The high salinity of soil, nutrient scarcity, and poor aggregate structure limit the exploitation and utilization of coastal mudflat resources and the sustainable development of saline soil agriculture. In this paper, the effects of applying exogenous organic acids combined with biological substrate on the composition and diversity of soil bacterial community were studied in moderately saline mudflats in Jiangsu Province. Methods: A combination of three exogenous organic acids (humic acid, fulvic acid, and citric acid) and four biological substrates (cottonseed hull, cow manure, grass charcoal, and pine needle) was set up set up on a coastal saline mudflat planted with a salt-tolerant forage grass, sweet sorghum. A total of 120 kg ha-1 of organic acids and 5,000 kg ha-1 of substrates were used, plus two treatments, CK without application of organic acids and substrates and CK0 in bare ground, for a total of 14 treatments. Results: No significant difference was found in the alpha diversity of soil bacterial community among all treatments (p ≥ 0.05), with the fulvic acid composite pine needle (FPN) treatment showing the largest increase in each index. The beta diversity differed significantly (p < 0.05) among all treatments, and the difference between citric acid-grass charcoal (CGC) and CK treatments was greater than that of other treatments. All treatments were effective in increasing the number of bacterial ASVs and affecting the structural composition of the community. Citric acid-cow manure (CCM), FPN, and CGC treatments were found to be beneficial for increasing the relative abundance of Proteobacteria, Chloroflexi, and Actinobacteria, respectively. By contrast, all treatments triggered a decrease in the relative abundance of Acidobacteria. Conclusion: Among the 12 different combinations of exogenous organic acid composite biomass substrates applied to the coastal beach, the CGC treatment was more conducive to increasing the relative abundance of the salt-tolerant bacteria Proteobacteria, Chloroflexi and Actinobacteria, and improving the community structure of soil bacteria. The FPN treatment was more conducive to increase the species diversity of the soil bacterial community and adjust the species composition of the bacterial community.

Intensive blood pressure lowering and the risk of new-onset diabetes in patients with hypertension: a post-hoc analysis of the STEP randomized trial.

AIMS: The strategy of blood pressure intervention in the elderly hypertensive patients (STEP) trial reported the cardiovascular benefit of intensive systolic blood pressure (SBP) control in patients with hypertension. The association between intensive SBP lowering and the risk of new-onset diabetes is unclear. This study aimed to evaluate the effect of intensive SBP lowering on the incidence of new-onset diabetes. METHODS AND RESULTS: Participants in STEP who had baseline fasting serum glucose (FSG) concentrations <7.0 mmol/L and no history of diabetes or hypoglycaemic medication use were included. The primary outcome was new-onset diabetes defined as the time to first occurrence of FSG concentrations ≥7.0 mmol/L. The secondary outcome was new-onset impaired fasting glucose (FSG: 5.6-6.9 mmol/L) in participants with normoglycemia. A competing risk proportional hazards regression model was used for analysis. The cohort comprised 5601 participants (mean age: 66.1 years) with a mean baseline SBP of 145.9 mmHg. Over a median follow-up of 3.42 years, 273 (9.6%) patients in the intensive SBP group (target, 110 to <130 mmHg) and 262 (9.5%) in the standard SBP group (target, 130 to <150 mmHg) developed diabetes (adjusted hazard ratio, 1.01; 95% confidence interval (CI), 0.86-1.20). The adjusted hazard ratio for the secondary outcome was 1.04 (95% CI, 0.91-1.18). The mean highest FSG concentration during the follow-up was 5.82 and 5.84 mmol/L in the intensive and standard groups, respectively. CONCLUSION: Intensive SBP lowering is not associated with an altered risk of new-onset diabetes or impaired fasting glucose in hypertensive patients. REGISTRATION: STEP ClinicalTrials.gov, number: NCT03015311.

There is no significant association between intensive SBP lowering and the risk of new-onset diabetes or impaired fasting glucose in hypertensive patients aged 60­80 years.Our findings improve the understanding of the benefits and risks of implementing an intensive SBP treatment strategy in the clinic for older hypertensive patients.Our findings suggest that clinicians should continue to implement intensive SBP lowering strategies, without worrying about an altered risk of new-onset diabetes in their patients.

Biomass composite with exogenous organic acid addition supports the growth of sweet sorghum (Sorghum bicolor 'Dochna') by reducing salinity and increasing nutrient levels in coastal saline-alkaline soil.

Introduction: In coastal saline lands, organic matter is scarce and saline stress is high. Exploring the promotion effect of intervention with organic acid from biological materials on soil improvement and thus forage output and determining the related mechanism are beneficial to the potential cultivation and resourceful, high-value utilization of coastal mudflats as back-up arable land. Method: Three exogenous organic acids [humic acid (H), fulvic acid (F), and citric acid (C)] were combined with four kinds of biomass materials [cottonseed hull (CH), cow manure (CM), grass charcoal (GC), and pine needle (PN)] and applied to about 0.3% of medium-salt mudflat soil. The salinity and nutrient dynamics of the soil and the growth and physiological differences of sweet sorghum at the seedling, elongation, and heading stages were observed under different treatments to screen for efficient combinations and analyze the intrinsic causes and influencing mechanisms. Results: The soil salinity, nutrient dynamics, and forage grass biological yield during sweet sorghum cultivation in saline soils differed significantly (p < 0.05) depending on the type of organic acid-biomass composite applied. Citric acid-pine needle composite substantially reduced the soil salinity and increased the soil nutrient content at the seedling stage and improved the root vigor and photosynthesis of sweet sorghum by increasing its stress tolerance, allowing plant morphological restructuring for a high biological yield. The improvement effect of fulvic acid-pine needle or fulvic acid-cow manure composite was manifested at the elongation and heading stages. Discussion: Citric acid-pine needle composite promoted the growth of saline sweet sorghum seedlings, and the effect of fulvic acid-pine needle composite lasted until the middle and late stages.

The Influence of baseline glycemic status on the effects of intensive blood pressure lowering: Results from the STEP randomized trial.

BACKGROUND: Intensive systolic blood pressure (SBP) lowering showed cardiovascular benefits in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. We investigated whether baseline glycemic status influences the effects of intensive SBP lowering on cardiovascular outcomes. METHODS: In this post hoc analysis of the STEP trial, participants were randomly assigned to receive intensive (110 to <130 mmHg) or standard SBP treatment (130 to <150 mmHg) and categorized by baseline glycemic status into three subgroups: normoglycemia, prediabetes, and diabetes. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. A competing risk proportional hazards regression model was used in the analysis. RESULTS: Of the 8,318 participants, 3,275, 2,769, and 2,274 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 3.33 years, intensive SBP lowering significantly reduced the risk of the primary outcome (adjusted hazard ratio 0.73, 95% confidence interval [CI] 0.59-0.91). The adjusted hazard ratios for the primary outcome in the normoglycemia, prediabetes, and diabetes subgroups were 0.72 (95% CI 0.49-1.04), 0.69 (95% CI 0.46-1.02), and 0.80 (95% CI 0.56-1.15), respectively. The intensive SBP lowering strategy resulted in similar effects among participants in the three subgroups (all interaction P >0.05). The sensitivity analyses showed consistent results with the main analysis. CONCLUSION: The effects of intensive SBP lowering on cardiovascular outcomes were consistent among participants with normoglycemia, prediabetes, and diabetes.

Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Blood Pressure Lowering: Results From the STEP Randomized Trial.

BACKGROUND: The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial demonstrated that intensive systolic blood pressure (SBP) lowering has cardiovascular benefits. However, the influence of baseline diastolic blood pressure (DBP) on the effects of intensive blood pressure lowering on cardiovascular outcomes has not been fully elucidated. METHODS: We performed a post hoc analysis of the STEP trial. Participants were randomly allocated to intensive (110 to <130 mm Hg) or standard (130 to <150 mm Hg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and cardiovascular death), major adverse cardiac event (a composite of the individual components of the primary outcome except for stroke), and all-cause mortality were analyzed according to baseline DBP as both a categorical and a continuous variable. RESULTS: The 8259 participants had a mean age of 66.2±4.8 years, and 46.5% were men. Participants with lower DBP were slightly older and had greater histories of cardiovascular disease, diabetes, and hyperlipidemia. Within each baseline DBP quartile, the mean achieved DBP was lower in the intensive versus standard group. The effects of intensive SBP lowering were not modified by baseline DBP as a continuous variable or as a categorical variable (quartiles, or <70, 70 to <80, and ≥80 mm Hg; all P value for interaction >0.05). CONCLUSIONS: The beneficial effects of intensive SBP lowering on cardiovascular outcomes were unaffected by baseline DBP. Lower DBP should not be an obstacle to intensive SBP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.